crossing96/oncoscreening huggingface dataset:
ALT-803 in the treatment of non-muscle-invasive bladder cancer: Preclinical and clinical evidence and translational potential.	Bladder cancer (BCa) is one of the most common malignant tumors that cause death. Approximately 75%-85% of BCa develop into non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette-Guérin (BCG) is the gold standard for avoiding cystectomy in the treatment of NMIBC. Unfortunately, up to 30% of patients do not respond to BCG treatment, and up to 70% of BCG responders relapse. The United States Food and Drug Administration (FDA) approved valrubicin (1998) and pembrolizumab (2020) for the treatment of BCG-unresponsive (BCGu) NMBIC. However, the complete remission rate for valrubicin and pembrolizumab was only 16% and 40.6%, respectively. ALT-803 (N-803) is an IL-15 superagonist and reduces tumor burden by promoting the proliferation and activation of NK cells and CD8(+) T cells. The FDA received (23 May 2022) and accepted to review (28 July 2022) the marketing submission of ALT-803 plus BCG for the treatment of BCGu NMIBC. However, the FDA previously rejected the application for oportuzumab monatox (OM) due to a lack of data comparing it with pembrolizumab on August 20, 2021. Interestingly, the clinical efficacy and safety of ALT-803 were higher than that of pembrolizumab and OM, suggesting that ALT-803 may be approved by FDA. This review aims to further knowledge of the preclinical and clinical evidence of ALT-803 in the treatment of NMIBC and discuss its translational potential.	bladder
Identification and validation of novel biomarkers affecting bladder cancer immunotherapy via machine learning and its association with M2 macrophages.	BACKGROUND: Immunotherapy has shown promising results in bladder cancer therapy options. METHODS: Analysis of open-access data was conducted using the R software. Open-access data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and IMvigor210 databases. Immunofluorescence and co-culture systems were utilized to validate the effect of PTHLH on M2 macrophage polarization. RESULTS: Here, through the combined (TCGA, GSE128959, GSE13507, and GSE83586) and IMvigor210 cohorts, we comprehensively investigated the biological and immune microenvironment differences in patients with diverse immunotherapy responses. Meanwhile, we found that M2 macrophage could affect bladder cancer immunotherapy sensibility. Moreover, based on the machine learning algorithm (LASSO logistics regression), PTHLH, BHMT2, and NGFR were identified, which all have good prediction abilities for patient immunotherapy. Then, a logistics regression model was established based on PTHLH, BHMT2, and NGFR, and each patient was assigned a logistics score. Subsequently, we investigated the difference in patients with high low logistics scores, including biological enrichment, immune microenvironment, and genomic characteristics. Meanwhile, data from the Human Protein Atlas database indicated a higher protein level of PTHLH in bladder cancer tissue. Immunofluorescence indicated that the knockdown of PTHLH in bladder cancer cells can significantly inhibit the M2 polarization of co-culture M0 macrophages. CONCLUSIONS: Our study investigated the difference between bladder cancer immunotherapy responders and non-responders. Meanwhile, the PTHLH was identified as a novel biomarker for bladder cancer immunotherapy.	bladder
Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy.	OBJECTIVE: To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU. METHODS: Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL). RESULTS: A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P = .036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P = .08). CONCLUSIONS: Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state.	bladder
Adherence to Mediterranean-Style Dietary Pattern and Risk of Bladder Cancer: A Case-Control Study in Iran.	Few dietary patterns are related to reduce the Bladder Cancer (BC) risk. One of the well-known dietary patterns is the Mediterranean diet (MD). This case-control study investigated the association between MD and the odds of BC among Iranian population. The present case-control study was performed on 103 eligible cases and 200 controls age 45 to 92 years. Diet of participants was assessed by a validated 168-item food frequency questionnaire (FFQ). Adherence to MD was measured by Mediterranean-Style Dietary Pattern Score (MSDPS). Multivariate logistic regression was used to estimate the relationship between MSDPS and risk of BC. After controlling for potential confounders, a negative association was observed between MSDPS and risk of BC (OR = 0.22; 95%CI = 0.09-0.52; p trend = 0.001). Furthermore, significant negative associations were observed for dairy, fish and other seafood, whole-grain, bread intake and risk of BC (p for trend < 0.05). In contrast, the risk of BC increased for high intake of poultry (OR = 1.09; 95%CI = 1.03-1.15; p trend = 0.003), sweets (OR = 1.24; 95%CI = 1.03-1.48; p trend = 0.018) and egg (p for trend = 0.01). Our results suggested that dietary habit in concordance with the principles of the Mediterranean dietary pattern may protect against BC.	bladder
NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo.	BACKGROUND: NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. METHODS: In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationship between NEAT1 and the prognosis of patients with bladder cancer was analysed. In vitro experiments explored the effects of NEAT1 on biological behaviours of bladder cancer T24 and 5637 cells. Bioinformatics prediction and luciferase assays were used to assay the regulatory mechanism of action of NEAT1 and miR-101. Loss and gain of the expression of miR-101 and VEGF-C were used to explore the effects of the NEAT1/miR-101/VEGF-C pathway on T24 and 5637 cells. The effect of NEAT1 on the growth of bladder cancer in vivo was explored using an orthotopic tumourigenesis model. RESULTS: NEAT1 and VEGF-C were significantly upregulated in bladder cancer samples, and miR-101 was significantly downregulated. NEAT1 upregulation was associated with poorer recurrence-free survival of patients with bladder cancer. Overexpression of NEAT1 promoted the proliferation, migration and invasion of bladder cancer cells. The results of the luciferase assay indicated that miR-101 was a target of NEAT1. The promoting effects of NEAT1 on bladder cancer cells were reversed by miR-101 upregulation, and inhibition of miR-101 enhanced the effects of NEAT1. Overexpression of VEGF-C had a clear synergistic effect with the action of NEAT1. Overexpression of NEAT1 increased tumour growth and induced the development of liver metastasis. CONCLUSIONS: In conclusion, our data indicated that NEAT1 was expressed at high levels in bladder cancer patients and correlated with unfavourable prognosis. NEAT1 promoted malignant development of bladder cancer in vitro and in vivo by regulating the miR-101/VEGF-C pathway.	bladder
Lectin-Based Study Reveals the Presence of Disease-Relevant Glycoepitopes in Bladder Cancer Cells and Ectosomes.	Bladder cancer is a malignancy that remains a therapeutic challenge and requires the identification of new biomarkers and mechanisms of progression. Several studies showed that extracellular vesicles promote angiogenesis, migration and metastasis, and inhibit apoptosis in bladder cancer. This effect may depend on their glycosylation status. Thus, the aim of this study was to compare glycosylation profiles of T-24 urothelial bladder cancer cells, HCV-29 normal ureter epithelial cells, and ectosomes released by both cell lines using lectin blotting and flow cytometry. Ectosomes displayed distinct total and surface glycosylation profiles with abundance of β-1,6-branched glycans and sialilated structures. Then, it was investigated whether the glycosylation status of the T-24 and HCV-29 cells is responsible for the effect exerted by ectosomes on the proliferation and migration of recipient cells. Stronger proproliferative and promigratory activity of T-24-derived ectosomes was observed in comparison to ectosomes from HCV-29 cells. When ectosomes were isolated from DMJ-treated cells, the aforementioned effects were diminished, suggesting that glycans carried by ectosomes were involved in modulation of recipient cell function. HCV-29- and T-24-derived ectosomes also increased the viability and motility of endothelial HUVEC cells and Hs27 fibroblasts. This supports the hypothesis that ectosomes can modulate the function of various cells present in the tumor microenvironment.	bladder
TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region.	Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18/31), C250T (4/31), and C158A (1/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.	bladder
Conditional survival after radical cystectomy for non-metastatic muscle-invasive squamous cell carcinoma of the urinary bladder: A population-based analysis.	PURPOSE: To assess the effect of event-free survival duration on cancer-specific mortality (CSM) after radical cystectomy (RC) in nonmetastatic muscle-invasive squamous cell carcinoma of the urinary bladder. METHODS: RC patients treated for non-metastatic muscle-invasive squamous cell carcinoma of the urinary bladder were identified within the Surveillance, Epidemiology, and End Results database (2000-2018). Independent predictor status for CSM of T and N stage groupings (i.e., T2N0, T3N0, T4N0, and TanyN1-3) was tested in multivariable Cox-regression models. Conditional 5-year CSM-free estimates were assessed at baseline and at 4 specific event-free survival times (i.e. 6, 12, 18 and 24 months), within each of the 4 examined stage groups. RESULTS: Of 981 RC patients, 206 (21%), 416 (42%), 152 (16%), and 207 (21%) were T2N0, T3N0, T4N0, and TanyN1-3, respectively. In multivariable Cox-regression models T3N0 (HR 1.94), T4N0 (HR 5.22), and TanyN1-3 (HR 6.62) were independent predictors of CSM, relative to T2N0. In conditional survival analyses based on 24 months event-free status, survival estimates were: 89% for T2N0 vs. 76% at baseline (Δ = 13%), 84% for T3N0 vs. 58% at baseline (Δ = 26%), 69% for T4N0 vs. 25% at baseline (Δ = 44%), 69% for TanyN1-3 vs. 22% at baseline (Δ = 47%). CONCLUSIONS: Event-free status at 24 months of follow-up is associated with substantially higher CSM-free survival than when CSM-free survival is predicted at baseline. The magnitude of this effect is most pronounced in TanyN1-3 and T4N0 patients, intermediate in T3N0 and more modest, nonetheless important, in T2N0.	bladder
Metabolic acidosis after ileal urinary diversion and radical cystectomy. Do we know as much as we think we do? A systematic review.	Urine contact with the mucosa of the urinary diversion (UD) after radical cystectomy (RC) produces different ion exchanges that favor the development of metabolic acidosis (MA). This phenomenon is a frequent cause of hospital readmission and short/long-term complications. We performed a systematic review of MA in RCs with ileal UD, analyzing its prevalence, diagnosis, risk factors and treatment. We systematically searched Pubmed® and Cochrane Library for original articles published before May 2022 according to PRISMA guidelines. A total of 421 articles were identified. We selected 25 studies that met the inclusion criteria involving 5811 patients. Obtaining precise data on the prevalence of MA is difficult, largely due to the heterogeneity of the diagnostic criteria used given the diversity of studies analyzed. Development of MA is multifactorial. In the early period, MA is more prevalent in patients with UD with longer ileal segments, better urinary continence, and impaired renal function. Age and diabetes are risk factors associated with MA in later periods. MA is the most common cause of second or more hospital readmissions. Prophylaxis with oral bicarbonate for three months in patients at risk could improve these results. Although MA after ileal UD is a well-known condition, this review highlights the need to implement homogeneous criteria for the diagnosis, follow-up, and treatment, in addition to protocolizing prevention/prophylaxis strategies in patients at risk.	bladder
Biological Stratification of Invasive and Advanced Urothelial Carcinoma.	Muscle-invasive urothelial carcinoma (UC) of the bladder remains a highly lethal malignancy. In this review the authors explore the underlying biology associated with the evolution from non-muscle-invasive UC to muscle-invasive and metastatic UC, with a special focus on the molecular stratification of UC and the potential of this stratification to be used for treatment selection.	bladder
Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer.	The purpose of this study was to explore the relationship between bladder urothelial cancer (BLCA) and immunity, to screen prognosis-related immune genes (PIGs), and to construct an immune-related prognosis model (IRPM). We processed the relevant data of The Cancer Genome Atlas (TCGA-BLCA) and GSE13507 using R software and Perl. We divided BLCA into high-immunity and low-immunity subtypes. There were significant differences in the two subtypes. In addition, we identified 13 PIGs of BLCA by jointly analyzing the gene expression data and survival information of GSE13507 and TCGA-BLCA, and constructed IRPM through nine of them. The low-risk group had better survival outcome than the high-risk group. We also constructed a nomogram based on clinicopathological information and risk scores of the patients. Moreover, the prognosis of BLCA patients was significantly impacted by the expression of almost every gene used to calculate the risk score. The result of real-time fluorescence quantitative polymerase chain reaction revealed that all the genes used to calculate the risk score were differentially expressed between BLCA and adjacent normal tissues, except PDGFRA. Our research provided potential targets for the treatment of BLCA and a reference for judging the prognosis of BLCA.	bladder
Clinical outcomes following laparoscopic radical nephroureterectomy in octogenarians.	BACKGROUND: This study aimed to compare the incidence of postoperative complications occurring within 30 days of surgery between octogenarians and younger patients and identify preoperative risk factors for the incidence of postoperative complications. Moreover, we also compared the oncological outcomes between octogenarians and younger patients. METHODS: This retrospective study included 283 patients who underwent laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma from 2002 to 2020. The patients were divided into octogenarians and younger patients (age: < 80 years), and their clinical characteristics, perioperative parameters, and postoperative complications were evaluated. The predictors of postoperative complications were evaluated using logistic regression models. Recurrence-free survival, cancer-specific survival, and overall survival were measured using the Kaplan-Meier method. RESULTS: Twelve (17.1%) octogenarians and 40 (18.7%) younger patients had postoperative complications. No significant difference in the incidence of postoperative complications was observed between octogenarians and younger patients (p = 0.14). A high body mass index was a significant risk factor for complications (p = 0.03). The 5-year recurrence-free survival, cancer-specific survival, and overall survival rates for octogenarians and younger patients were 72% and 64% (p = 0.31), 76% and 63% (p = 0.63), and 43% and 63% (p = 0.06), respectively. CONCLUSION: Laparoscopic radical nephroureterectomy can be performed in octogenarians with complication rates similar to those in younger patients. Similarly, the outcomes of laparoscopic radical nephroureterectomy for oncological control do not differ significantly between octogenarians and younger patients. This procedure is safe and effective for selected octogenarians.	bladder
Progress in the treatment of urethral adenocarcinoma.	BACKGROUND: Urothelial adenocarcinoma (UA) is a rare subtype of primary urothelial carcinoma, which is more common in women and has a poor prognosis. Because of their low incidence, most of the existing literature is based on case reports and there is a lack of comprehensive literature on this type of tumor. PURPOSE: This article provides a comprehensive and systematic review of the epidemiology, pathological types, treatment, and prognosis of UA. Especially in the treatment section, we reviewed the various treatment methods including surgery, radiotherapy, chemotherapy, immunotherapy and molecular targeted therapy. This review aims to provide a theoretical basis for the clinical diagnosis and management of UA. METHODS: We reviewed the relevant literature of UA from Pubmed. CONCLUSION: There is no standard treatment for UA. Multidisciplinary therapy, including surgery, radiotherapy and chemotherapy, is the current trend. Immunotherapy and molecular targeted therapy will also become viable options for the treatment of UA in future.	bladder
Tissue S100/calgranulin expression and blood neutrophil-to-lymphocyte ratio (NLR) in dogs with lower urinary tract urothelial carcinoma.	BACKGROUND: Urothelial carcinoma (UC) is the most common neoplasm of the canine lower urinary tract, affecting approximately 2% of dogs. Elderly female patients of certain breeds are predisposed, and clinical signs of UC can easily be confused with urinary tract infection or urolithiasis. Diagnosis and treatment are challenging given the lack of disease-specific markers and treatments. The S100A8/A9 complex and S100A12 protein are Ca(2+)-binding proteins expressed by cells of the innate immune system and have shown promise as urinary screening markers for UC. The neutrophil-to-lymphocyte ratio (NLR) can also aid in distinguishing certain neoplastic from inflammatory conditions. Our study aimed to evaluate the tissue expression of S100/calgranulins and the blood NLR in dogs with UC. Urinary bladder and/or urethral tissue samples from dogs with UC (n = 10), non-neoplastic inflammatory lesions (NNUTD; n = 6), and no histologic changes (n = 11) were evaluated using immunohistochemistry. Blood NLRs were analyzed in dogs with UC (n = 22) or NNUTD (n = 26). RESULTS: Tissue S100A12-positive cell counts were significantly higher in dogs with lower urinary tract disease than healthy controls (P = 0.0267 for UC, P = 0.0049 for NNUTD), with no significant difference between UC and NNUTD patients. Tissue S100A8/A9-positivity appeared to be higher with NNUTD than UC, but this difference did not reach statistical significance. The S100A8/A9(+)-to-S100A12(+) ratio was significantly decreased in neoplastic and inflamed lower urinary tract tissue compared to histologically normal specimens (P = 0.0062 for UC, P = 0.0030 for NNUTD). NLRs were significantly higher in dogs with UC than in dogs with NNUTD, and a cut-off NLR of ≤ 2.83 distinguished UC from NNUTD with 41% sensitivity and 100% specificity. Higher NLRs were also associated with a poor overall survival time (P = 0.0417). CONCLUSIONS: These results confirm that the S100/calgranulins play a role in the immune response to inflammatory and neoplastic lower urinary tract diseases in dogs, but the tissue expression of these proteins appears to differ from their concentrations reported in urine samples. Further investigations of the S100/calgranulin pathways in UC and their potential as diagnostic or prognostic tools and potential therapeutic targets are warranted. The NLR as a routinely available marker might be a useful surrogate to distinguish UC from inflammatory conditions.	bladder